Serum
ferritin is present in two forms--a glycosylated form that results from active secretion by cells and a nonglycosylated form that is directly released by damaged cells.
Glycosylated ferritin binds to
concanavalin A (Con A) through the
glucose and/or
mannose residues of the molecule. Patients with
neuroblastoma frequently present at diagnosis with abnormally elevated levels of serum
ferritin. The
ferritin levels will, however, return to normal with clinical remission, suggesting that the
tumor is the origin of the elevated
ferritin. With the use of a Con A binding assay, an investigation was made as to whether the increased levels of serum
ferritin at diagnosis in
neuroblastoma patients resulted from active secretion by the
tumor or were the consequence of direct release of
ferritin from damaged tissue. Serum samples were collected at diagnosis from 36 children with
neuroblastoma and from 16 normal healthy subjects. Tissue
ferritins were purified from normal human liver, placenta, HeLa cells, human
neuroblastoma, and
hepatoma cells grown in culture. Serum and tissue
ferritins were measured before and after binding with Con A. Sixty-three percent of serum
ferritin from
neuroblastoma patients and 66% of serum
ferritin from normal subjects were bound to Con A, suggesting that they were glycosylated and were likely to have been secreted. On the other hand, only 28% of tissue
ferritin were bound to Con A. Furthermore, most patients showed abnormally elevated levels of serum
ferritin, and 63% of these
ferritins were bound to Con A. These results are compatible with the hypothesis that much of the elevated
ferritin in sera of patients with
neuroblastoma seen at diagnosis is the result of secretion of
ferritin by the
tumor.